The difference is most likely due to the weight that you are using in your hand
calculation. Because creatinine is produced by muscle tissue, C&G recommend that you
use lean body weight, except in morbidly obese patients. Because creatinine is
produced by muscle tissue, not fat, additional weight in form of fat does not significantly
alter the production of creatinine.

Must I always use steady-state analysis? For example, my patient received 2 doses of 1gm vanco q12hr, and for some reason the dose was decreased to 600mg around which levels were drawn.

You do not have to assume steady-state if you use the 3-point method.
Draw a trough before the 600mg dose, a peak after, then a mid-point level after that.
The program will use the pre-dose trough and the peak level to calculate the volume of
distribution. The two post-dose levels are used to calculate the elimination rate.

Why is the default dose for once-a-day gentamicin 5mg/kg instead of Hartford's 7mg/kg?

Please refer to this consensus document which appeared in the June 1997 issue of the
International J. of Clinical Pharmacology and Therapeutics:

In many respects the approach of the Hartford nomogram is just as simplistic as giving
80mg Q 8 hours to all patients with a "normal" serum creatinine. Instead, all patients
should be individually dosed in order to maximize therapeutic efficacy and minimize the
risk of toxicity. The patient should receive a large enough dose to produce a peak level
that is 8 to 10 times greater than the MIC. The dosing interval should then be extended
to produce a trough less than 0.5 mcg/ml in order to provide a washout of aminoglycoside
in the renal tubule thereby reducing toxicity.

During prospective dosing of pediatric patients there seems to be no way to chose an initial target peak/trough value like there is for adults.

The initial pediatric calculations are weight based, as they are in every
pediatric reference book you will find. Although you cannot target a specific peak
and trough, the program will show estimated peak and trough levels from your
selected dose.

The reason that initial doses are weight-based is because the creatinine clearance
equations for peds are not accurate enough to be used for pk modeling.

Do I enter serum level times relative to the beginning or the end of the infusion?

Times are relative the beginning and the end of the infusion.

For pre-dose times, this refers to the beginning of the infusion, hence the instruction "minutes BEFORE infusion".

For post-dose times, this refers to the end of the infusion, hence the instruction "hours AFTER infusion".

How does the program handle late doses?

Unfortunately, late doses can not be avoided, so how can you use these levels?
There are at least two late dose scenarios, each would be handled differently,
depending on the methodology you are using.

The first late dose scenario we'll describe occurs if the dose was late but the levels were
correctly drawn relative to the actual hang time. For example, the nurse is supposed to be giving
gent 80mg Q 8 hours, at 6-14-22, but the sample dose is given late, at 1600. The trough was
drawn at 1530 and the peak at 1730. As you can see, the levels are correctly drawn relative
to the late dose.

First, let's examine the Sawchuk and Zaske method. This method is the gold standard for evaluation of
peak and trough levels in the one-compartment open model. Sawchuk and Zaske drew three levels: a trough
before the dose, a peak after the dose, and another trough after the dose. However, many institutions take
a shortcut and only draw two levels, a trough before the dose and a peak after. If the patient is at
steady-state, then you can assume that the second trough after the dose will be the same as the trough
before the dose. Under most circumstances, this is a valid assumption and will save laboratory expenses.

Next, look at Sawchuk and Zaske's equations for calculating pk parameters, you can find them in the program
help file (Press the F1 key). Where is the dosing interval in these equations? ...... nowhere!
The dosing interval is not used in any calculation.

If you are using the 3-point method, the interval is not used, and it doesn't matter if the dose was
given late, as long as the levels are correctly drawn, relative to the time the dose was actually given.

The second late dose scenario occurs when the dose is give late and the levels are correctly
drawn relative to the scheduled hang time, not the actual hang time. For example, if the nurse
is supposed to be giving gent 80mg Q 8 hours, at 6-14-20, the sample dose is given late, at 1600, but
the trough was drawn at 1330 and the peak at 1530. As you can see the levels are correctly drawn relative
to the scheduled dose, not the actual hang time, the "peak" is not a peak at all, but a trough drawn
before the dose was given.

This scenario is the result of a lack of communication between lab and nursing. In this case,
throw out the peak and just use the trough. With Bayesian you only need a single trough level.

How do I enter my own drug model?

Where I can find linear regression equations for beta-lactam antibiotics? I'd like to be able to get a good set of Kel values to plug in for cephalosporins and penicillins.

Unfortunately, this information is not found in one single reference.
Bennett's Drug Prescribing in Renal Failure and Chernow's
Critical Care Pharmacotherapy have tables of pk data for common
drugs. The FDA package insert of newer drugs usually has an excellent
pharmacokinetics section.

For a detailed tutorial on creating one compartment models, please
see this page:

We sometimes see an "outlier" message when analyzing serum levels with Bayesian, what does this mean?

Bayesian places significant weight on the population model. Because of this reliance
on the population model, it is very important with Bayesian that you pick the right
model for your patient. This is a particular problem with vancomycin because of the
*extreme* inter-patient variability in pk parameters.

When the program flags an "outlier", it means that, for whatever reason, the serum
levels can't be statistically reconciled with the population model. If, after 100
iterations, the Bayesian object (sum of least squares) is not reduced, it gets kicked
out of the loop and the patient is labeled an outlier.

Outliers are especially challenging when we are analyzing a single trough level.
If the patient's trough is out of range, then you need to get a truer picture of the
patient's pk parameters by measuring a peak and trough series instead of a
single trough.

If a significant percentage of your patients are flagged as outliers, then there is
a good possibility that the model you are using is not appropriate for your patient
population. This is a situation where the population analysis tool would be helpful.
Each time you print a consult based on serum level data, the calculated pk parameters
are saved. This data is a virtual gold mine of information about your patient population.
With this tool you can derive a model better fitted to your patients.

My patient is a double amputee, the program won't let me enter his height (36"), what should I do?

The program does not make any specific adjustments for amputees, so you'll need to
do some calculations the old-fashioned way. Enter the patient's pre-amputation
height. The program will calculate a baseline lean body weight.

Because creatinine is produced by lean tissue, to get a more accurate estimate of CrCl,
you'll need to estimate post-amputation muscle mass. Start with the LBW calculated from
the patient's pre-amputation height. Then deduct a percentage depending on the extent of
the amputation:

Hand - Decrease LBW by 0.7%

Forearm and hand - Decrease LBW by 2.3%

Total arm - Decrease LBW by 4.9%

Foot - Decrease LBW by 1.5%

Calf and foot - Decrease LBW by 5.8%

Total leg - Decrease LBW by 16%

In this case, since your patient is a double amputee, you would decrease the LBW
by 32%. Let's call this the Amputee-Adjusted LBW (AALBW).

If the patient's actual weight is less than the AALBW, then the patient is underweight
and you should use the patient's current weight to calculate CrCl.

If the patient weighs more than the AALBW, then you should hand calculate the
CrCl using the AALBW.

References

John Murphy's Clinical Pharmacokinetics, 2nd ed. 2001

Brunnstrom, S. Clinical kinesiology. 4th ed. 1983

My patient is bedridden and I cannot obtain his/her height, what should I do?

That is a good question. A patient may also have scoliosis or severe contractions
that prevent a true height measurement. There are (at least) three methods
that may be used to estimate height when actual measurement is not possible:
knee height, forearm length and demi-span.

What does the message "Y-intercept less than zero" mean when I try to perform population analysis?

"Y-intercept less than zero" is displayed when the regression line intercepts the Y axis below zero.
"Regression analysis yielded a negative slope" is displayed when the regression line is inverted.

The regression line is a plot of Y vs X where X is creatinine clearance (the independent variable) and Y
is the elimination rate (the dependent variable). The Y intercept is the Nonrenal Kel, the slope of the
regression line is the Renal Kel for the following equation:

Kel = NonRenalK + [CrCl x RenalK]

It would be impossible (of course) for there to be a negative slope or a negative NonRenal Kel, that would
mean you are somehow putting drug back into the system instead of excreting it.

Both of these "errors" are caused by a widely scattered data set for which a regression line cannot be
accurately calculated. This would be expected with a drug like Vancomycin which has a wide variability
in pk parameters. Usually it takes a higher N in your data set before the data becomes analyzable. Keep
saving your consults and eventually you will acquire a data set that will give usable results.

Desktop problem solutions

How and where do I download and install the update?

Click Check button to access the RxKinetics web site to check for available updates.

If an update is available, a confirmation dialog will appear. Click the "Yes" button.

Next, a change log dialog is displayed.

A running program cannot be replaced.
Therefore, you must exit APK before installing an update.
Web update will not proceed with the install step until you close APK.
After you have closed the APK program, click the "OK" button to begin the update process.

All versions of 64-bit Windows (XP, Vista, 7, 8, 10) are able to run 32-bit programs seamlessly through WOW64 which is
provided with the operating system and does not have to be explicitly enabled. In other words, it's 100% automatic.
(Ref: Microsoft)

According to Microsoft, 32-bit software running under WOW64 has a similar performance when executing under 32-bit Windows.
(Ref: Microsoft)

I click the APK icon and nothing happens. What gives?

Check the active task list in your Windows Task Manager (Ctrl+Alt+Del).
If it's there, then the APK window is off screen.
This behavior is sometimes triggered when you switch between different monitor resolutions and orientations.

We get an Error #33 (file lock violation) dialog and when we click OK the program stops running.

Error #33 (file lock violation) indicates one or more of the lock files are corrupt
or inaccessible. Lock files have the "@S@" extension and are used to keep track of
which records are open and which are locked for writing. Lock files are the gate-keepers
of the database, allowing multiple users to simultaneously access records without
corrupting the underlying data.

PalmOS problem solutions

Why do I need HotSync?

When I HotSync, only the patients from my Palm are added, not vice versa.

The default option is a one-way sync, from the Palm to the desktop.
Think of the Windows program as the data repository, containing the sum of all data.
The handheld, naturally, carries but a subset of patient data, it is a mobile data
gatherer if you will. In this scenario, there are multiple decentralized users of
Palms, but only one central repository of data, the desktop. The decentralized RPh's
are out and about, seeing patients, inputting data, calculating doses, writing consults.
At the end of the day, they HotSync to update the central database.

You may select a two-way synchronization on the preference screen of the Palm devices.
This allows you to have palms with different functions, some as data gatherers, others which
carry a full database of active patients.

If you use the Full Sync option, you must be diligent about keeping only active patients in
the desktop database. The patient database in the desktop version is divided into two tables:
one active, one inactive. The inactive table provides patient history, if you have a re-admit
you do not lose that previous data.

Keeping only your current patients active increases the manageability. It is difficult to manage
hundreds of patients on the Palm, there is no "seek" function, you only have the list to retrieve,
and it will get bogged down while listing hundreds of patients.

A good habit to get into is to print out a patient list once a week, and discharge those who are
no longer on service.

New patient and consult data from the Palm is not being added during the HotSync process.

Windows Mobile/Pocket PC problem solutions

Why do I need ActiveSync?

When I run APKsync, only the patients from my PDA are added, not vice versa.

The default option is a one-way sync, from the PDA to the desktop.
Think of the Windows program as the data repository, containing the sum of all data.
The handheld, naturally, carries but a subset of patient data, it is a mobile data
gatherer if you will. In this scenario, there are multiple decentralized users of
PDAs, but only one central repository of data, the desktop. The decentralized RPh's
are out and about, seeing patients, inputting data, calculating doses, writing consults.
At the end of the day, they synchronize their PDA's to update the central database.

You may select a two-way synchronization on the preference screen of the Pocket PC device.
This allows you to have palms with different functions, some as data gatherers, others which
carry a full database of active patients.

If you use the Full Sync option, you must be diligent about keeping only active patients in
the desktop database. The patient database in the desktop version is divided into two tables:
one active, one inactive. The inactive table provides patient history, if you have a re-admit
you do not lose that previous data.

Keeping only your current patients active increases the manageability. It is difficult to manage
hundreds of patients on the PDA, there is no "seek" function, you only have the list to retrieve,
and it will get bogged down while listing hundreds of patients.

A good habit to get into is to print out a patient list once a week, and discharge those who are
no longer on service.

Another workaround to this problem is to use a task switching program.
Once activated, the task switcher icon on the task bar enables you to see what
programs are currently running on your PDA and provides a way to switch between
running programs (and to shut down applications).

Some PDA manufacturers, like Dell, provide their own task switching program.
If your PDA did not come with a task switcher, HandySwitcher
is a 3rd party tool which works in a similar manner.